The present invention relates to the diagnosis of endothelial dysfunction, particularly in humans. The non-invasive technique involves blocking blood flow in a limb to stimulate endothelial function and then releasing the blood flow block to observe blood flow which is indicative of endothelial function. More specifically, the present invention relates to a method and apparatus for conducting such measurements by injecting a tracer substance and imaging or otherwise detecting the tracer ingress into the limb following the release of the blood flow block.
In recent years, the connection between endothelial dysfunction and the risk of atherosclerosis has been studied and established (see the article by Celermajer et al., xe2x80x9cNon-Invasive Detection of Endothelial Dysfunction in Children and Adults at Risk of Atherosclerosisxe2x80x9d, Lancet, 1992, Vol. 340, pages 1111 to 1115, and the article by Schxc3xa4chinger et al., xe2x80x9cPrognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Diseasexe2x80x9d, published in Circulation, 2000, Vol. 101, pages R1 to R8).
The most popular technique for measuring blood flow for the purposes of endothelial dysfunction in children and adults is the use of Doppler ultrasound which is able to obtain a measurement of blood flow in an artery of a patient non-invasively. As can be appreciated, this requires placing an ultrasound transceiver directly on top of an artery and the measurement accuracy is dependent on proper positioning of the ultrasound equipment with respect to the artery. The paper authored by Todd J. Anderson entitled xe2x80x9cAssessment and Treatment of Endothelial Dysfunction in Humansxe2x80x9d provides a review of known techniques for assessment of endothelial function in humans. These techniques include intracoronary studies, positron emission tomography, impedance plethysmography, brachial ultrasound (also known as Doppler ultrasound) and venous studies. This article was published in Vol. 34, Issue 3, (September 1999), pages 631-638 of JACC.
The fact that endothelial dysfunction is an indicator of coronary artery disease (CAD) makes the detection of endothelial dysfunction of great value in the diagnosis and treatment of the general population. People can be at risk of heart disease and CAD as a result of family history, environmental factors (such as the presence of first-hand or second-hand smoke), diet and age. The ability to provide for an efficient non-invasive test for the risk of atherosclerosis would be a valuable tool to determine whether more complex tests are needed to determine the presence of CAD or whether such further tests can be dismissed as unnecessary. Full coronary angiography consumes time on equipment costing in the range of $500,000 to $1,000,000, and require significant operator training and analysis by a skilled specialist. The cost savings to avoiding expensive tests is significant.
The ability to test endothelial dysfunction as an indicator of the state of CAD is also useful for the purposes of monitoring a patient""s response to medical treatment, i.e. drugs, diet, exercise, stress management, or a combination thereof.
It would therefore be desirable to provide for a test which would be reliable, easy to carry out, inexpensive and non-invasive for the purposes of determining endothelial dysfunction in humans.
It is an object of the present invention to provide an accurate method and apparatus for detecting endothelial dysfunction in humans which involves a comparatively low cost and is easy to carry out.
According to a first broad aspect of the invention, there is provided a method for diagnosing endothelial dysfunction by measuring tracer presence in arteries following the release of blood flow into the limb after a period of blockage of blood flow into the limb. According to one aspect of the invention, such blood flow is measured in a pair of laterally opposed limbs, preferably the forearms, and the tracer presence is compared between both limbs. The tracer is also preferably a radionuclide and the non-invasive measurement of the radionuclide is carried out by gamma ray detection.
According to another aspect of the invention, there is provided a device for guiding and mounting a person""s forearms over a detector measuring tracer presence within a region of interest in the forearm. In one embodiment, the guide is used for holding, in a predetermined position, a person""s forearm over a conventional 2-D gamma camera.
According to another embodiment, the guide is used to hold a person""s forearm in a fixed position with respect to a detector measuring the tracer presence in which the detector is located within a region of interest and is not required to form a two-dimensional image of the region of interest.
According to yet another embodiment of the invention, a detector for detecting radiation emitted from a radionuclide is provided within a band surrounding a person""s limb for detection of radiation.
It will be understood that several embodiments of the invention involve measuring tracer presence in two laterally opposed limbs of a person in which steps are taken to ensure that the sensitivity of measurement between both limbs is the same.
It will also be understood that several embodiments of the present invention involve the injection of a bolus of a radioactive tracer in a vein of a person. Preferably, the dosage strength of the radioactive tracer is measured by a detector prior to injection in order to obtain a reference calibration point. Preferably, the detector used for calibration is the detector used for measuring the tracer in both limbs.